In this issue of Molecular Cell, Guo et al. (2014) report that misfolded or aggregated nuclear proteins, such as pathogenic polyQ proteins, are cleared by a SUMO-dependent quality control pathway, which involves the E3 SUMO ligase PML and the SUMO-targeted ubiquitin ligase RNF4.

Sumo wrestling, Japan's national sport, have a long history over 300 years in Japan. Sumo is becoming wellknown all over the world as one of Japanese culture (Nagayama, 2008). As you know, professional Sumo wrestlers are expected to lead specific lifestyles that promote increases in body weight after go professional. This notion makes Sumo wrestlers a unique group of professional athletes unlik...

The purpose of this research was to identify a molecular clue to tumor proliferation in oral squamous cell carcinoma (SCC) and to test the value as a predictive marker for prognosis. In cDNA array analysis, small ubiquitin-related modifier-1 (SUMO-1) was expressed at much higher levels in oral SCC tissue and oral SCC cell lines than normal oral epithelium. The result was confirmed by RT-PCR ana...

The RGSZ2 gene, a regulator of G protein signaling, has been implicated in cognition, Alzheimer's disease, panic disorder, schizophrenia and several human cancers. This 210 amino acid protein is a GTPase accelerating protein (GAP) on Gαi/o/z subunits, binds to the N terminal of neural nitric oxide synthase (nNOS) negatively regulating the production of nitric oxide, and binds to the histidine t...

SUMOylation of transcription factors and chromatin proteins is in many cases a negative mark that recruits factors that repress gene expression. In this study, we determined the occupancy of Small Ubiquitin-like MOdifier (SUMO)-1 on chromatin in HeLa cells by use of chromatin affinity purification coupled with next-generation sequencing. We found SUMO-1 localization on chromatin was dynamic thr...

In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyze the nuclear trafficking dynamics of PML and its SUMO-dependent ubiquitin E3 ligase, RNF4 in res...

Chromosomal region maintenance 1 (CRM1) mediates p53 nuclear export. Although p53 SUMOylation promotes its nuclear export, the underlying mechanism is unclear. Here we show that tethering of a small, ubiquitin-like modifier (SUMO) moiety to p53 markedly increases its cytoplasmic localization. SUMO attachment to p53 does not affect its oligomerization, suggesting that subunit dissociation requir...

Small ubiquitin-like modifier (SUMO) proteins regulate many important eukaryotic cellular processes through reversible covalent conjugation to target proteins. In addition to its many well-known biological consequences, like subcellular translocation of protein, subnuclear structure formation, and modulation of transcriptional activity, we show here that SUMO-2 also plays a role in mRNA transla...

24 Small Ubiquitin like MOdifier (SUMO) is used by the intrinsic antiviral immune response to 25 restrict viral pathogens, such as Herpes Simplex Virus 1 (HSV-1). Despite characterization of 26 the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that 27 mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO 28 levels are largely...

RNF4 (RING finger protein 4) is a STUbL [SUMO (small ubiquitin-related modifier)-targeted ubiquitin ligase] controlling PML (promyelocytic leukaemia) nuclear bodies, DNA double strand break repair and other nuclear functions. In the present paper, we describe that the sequence and spacing of the SIMs (SUMO-interaction motifs) in RNF4 regulate the avidity-driven recognition of substrate proteins...